Biology subjects

Serrano, G. E.

Publications and source records attributed to Serrano, G. E..

3 recordsLinked to original sources

bioRxiv2019

A Modification of the Bielschowsky Silver Stain for Alzheimer Neuritic Plaques: Suppression of Artifactual Staining by Pretreatment with Oxidizing Agents

The Bielschowsky silver method has been the most commonly-used histological stain for demonstrating the neuritic plaques and neurofibrillary tangles that define Alzheimers disease (AD). The stain has been critical to providing a common measure allowing large clinicopathological correlation studies that have demonstrated statistically significant and independent contributions of both lesion types to cognitive impairment and dementia. The continuing relevance of neuritic plaques, and the Bielschowsky stain as the method of choice for their demonstration, is also indicated by its use as the US Food and Drug Administration (FDA) \"standard of truth\" for autopsy confirmation of the validity of PET amyloid imaging agents. Many modifications of the Bielschowsky stain have been published but it is still known to frequently generate artifactual staining that at times mimics the appearance of amyloid plaques. In this study we found that pretreatment with oxidizing agents prior to the initial incubation in silver nitrate eliminates these artifacts and reduces the commonly observed high background staining. This new method may be valuable for Alzheimers disease (AD) researchers and neuropathologists.

neuroscience↗

bioRxiv2019

Large-scale proteomic analysis of human prefrontal cortex identifies proteins associated with cognitive trajectory in advanced age

In advanced age, some individuals maintain a stable cognitive trajectory while others experience a rapid decline. Such variation in cognitive trajectory is only partially explained by traditional neurodegenerative pathologies. Hence, to identify new processes underlying variation in cognitive trajectory, we perform an unbiased proteome-wide association study of cognitive trajectory in a discovery (n=104) and replication cohort (n=39) of initially cognitively unimpaired, longitudinally assessed older-adult brain donors. We find 579 proteins associated with cognitive trajectory after meta-analysis. Notably, we present novel evidence for increased neuronal mitochondrial activities in cognitive stability regardless of the burden of traditional neuropathologies. Furthermore, we provide additional evidence for increased synaptic activities and decreased inflammation and apoptosis in cognitive stability. Importantly, we nominate proteins associated with cognitive trajectory, particularly the 38 proteins that act independently of neuropathologies and are also hub proteins of protein co-expression networks, as promising targets for future mechanistic studies of cognitive trajectory.

neuroscience↗

bioRxiv2019

Faster Cognitive Decline in Dementia due to Alzheimer Disease with Clinically Undiagnosed Lewy Body Disease

Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimers disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimers disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distribution and density thresholds for DLB. Although it has been established that ADD subjects with undifferentiated LBD have a more rapid cognitive decline than those with ADD alone, it is still unknown whether AD-LB subjects, who represent the majority of LBD and approximately one-third of all those with ADD, have a different clinical course. Subjects with dementia included those with \"pure\" ADD (n = 137), AD-DLB (n = 64) and AD-LB (n = 114), all with two or more complete Mini Mental State Examinations (MMSE) and a full neuropathological examination. Linear mixed models assessing MMSE change showed that the AD-LB group had significantly greater decline compared to the ADD group ({beta} = -0.69, 95% CI: -1.05, -0.33, p<0.001) while the AD-DLB group did not ({beta} = -0.30, 95% CI: -0.73, 0.14, p = 0.18). Of those with AD-DLB and AD-LB, only 66% and 2.1%, respectively, had been diagnosed with LBD at any point during their clinical course. The probable cause of LBD clinical detection failure is the lack of a sufficient set of characteristic core clinical features. Core DLB clinical features were not more common in AD-LB as compared to ADD. Compared with clinically-diagnosed AD-DLB subjects, those that were clinically undetected had significantly lower prevalences of parkinsonism (p = 0.046), visual hallucinations (p = 0.0008) and dream enactment behavior (0.013). Clinical identification of ADD with LBD would allow stratified analyses of ADD clinical trials, potentially improving the probability of trial success.

neuroscience↗